Management and Outcome of Microbial Anterior Scleritis Matthew A

CLINICAL SCIENCE

Management and Outcome of Microbial Anterior Scleritis Matthew A. Cunningham, MD, Jamie K. Alexander, BA, Alice Y. Matoba, MD, Dan B. Jones, MD, and Kirk R. Wilhemus, MD, PhD

microbial keratitis or panophthalmitis3,4 and has rarely Purpose: To evaluate the prevalence, predisposing factors, and occurred in the absence of contiguous disease.5 outcomes of bacterial and fungal scleritis. Microorganisms gain a direct portal of entry into the sclera from ocular trauma or surgery. For example, infections associated Methods: We reviewed the clinical findings, therapeutic inter- with scleral buckling material or sutures present as equatorial or ventions, and visual outcomes of patients with suppurative scleral posterior scleral inflammation.6 Focal infection of the anterior inflammation without preceding microbial keratitis who had micro- sclera also has developed after ocular surface surgery, radio- organisms isolated from scleral scrapings. therapy, or chemical exposure, often with a delayed onset.3 Design: Retrospective interventional case series. Exogenous microbial scleritis presents as a suppurative nodule, abscess, or ulcer. Reported causes include pathogens Results: Of 349 patients with scleritis diagnosed from 1999 to that are also responsible for microbial keratitis, such as Gram- 2009, 6 adults (1.7%) presented with suppurative inflammation of the negative rods, Gram-positive cocci, and filamentous fungi.5,7 anterior sclera due to Pseudomonas aeruginosa (2), Streptococcus Because of the relative rarity of scleral infections, we reviewed pneumoniae (2), Staphylococcus aureus (1), and Scedosporium our experience with bacterial and fungal scleritis over an apiospermum/Pseudallescheria boydii (1). Each had ocular surgery 11-year period to evaluate the clinical and visual outcomes of the affected eye before presentation. Intraocular extension occurred with medical and surgical management. in 2 eyes. After local and systemic antimicrobial therapy, all improved without evisceration or enucleation, and 4 attained vision of 20/60 or MATERIALS AND METHODS better. The clinical records of 349 patients with anterior scleritis, Conclusions: Bacterial or fungal scleritis is an uncommon ocular as categorized by diagnostic codes (379.00, 379.03, 379.04, infection that can belatedly follow anterior segment procedures. 379.06, or 379.09) of the International Classification of Diseases, Antimicrobial therapy and surgical intervention can success- Ninth Revision, who were treated at the Cullen Eye Institute fully control progressive suppuration and reduce vision-limiting between January 1999 and December 2009 were retrospectively complications. reviewed after authorization by the Baylor College of Medicine Institutional Review Board. Information on patients with culture- Key Words: infection, microbial scleritis, ocular microbiology, positive infection of the anterior sclera was collected from clinical, scleral graft photographic, and laboratory files. The dimensions of scleral (Cornea 2011;30:1020–1023) ulceration and suppuration obtained using an eyepiece reticule were used to estimate the elliptical area of scleral inflammation. Scleral scrapings were inoculated directly onto blood, chocolate, and Sabouraud agar plates, and microbial identification was based cleritis is an ocular manifestation of an immune-mediated on standard microbiological criteria. Culture positivity of scleral process. Reactive scleral inflammation occasionally arises S scrapings was defined as bacterial or fungal growth on 1 or more during the course of infectious diseases such as syphilis, primary culture media. Clinical data included previous surgery of tuberculosis, and zoster.1 Bacterial or fungal invasion into the the affected eye, initial and final Snellen visual acuity, sclera is uncommon, accounting for less than 1% of all eye inflammatory complications during follow-up, medical manage- infections.2 Scleral infection can develop during progressive ment, and surgical interventions. All patients who were diagnosed with scleritis were evaluated with a full review of systems, medical history (including systemic conditions associated with Received for publication August 9, 2010; revision received October 24, 2010; accepted November 27, 2010. scleral inflammation), and medication history. Cure was defined From the Cullen Eye Institute, Department of Ophthalmology, Baylor College as resolution of ocular inflammation during antimicrobial therapy of Medicine, Houston, TX. without recurrence after treatment was discontinued. Supported by a core grant (EY02520) from the National Eye Institute and by grants from the Sid W. Richardson Foundation and Research to Prevent Blindness, Inc. RESULTS The authors have no financial conflicts/proprietary interests in any products An average of 32 patients were diagnosed with scleritis, named in this article. either infective or immune-mediated, each year during the Reprints: Dr. K.R. Wilhelmus, Sid W. Richardson Ocular Microbiology Laboratory, Baylor College of Medicine, Department of Ophthalmology, study period. Six patients (1.7%), 4 men and 2 women who 6565 Fannin Street, Houston, TX 77030 (e-mail: [email protected]). were aged between 46 and 82 years (Table 1), had microbial Copyright Ó 2011 by Lippincott Williams & Wilkins infection of the anterior sclera without preceding microbial

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TABLE 1. Case Series of Microbial Scleritis Case/Sex/Age Previous Location Latent Initial Final Surgical (yrs)/Eye Pathogen Surgery (Area, mm2) Period* Vision Vision Intervention Complications 1/F/46/L S. pneumoniae Pterygium excision Nasal (12.5) 4 yrs 20/40 20/20 None Exudative retinal detachment, glaucomatous cupping 2/M/62/R S. pneumoniae Pterygium excision Nasal (82) 1 mo 20/80 20/40 Sclerectomy Nuclear sclerotic cataract 3/M/73/R P. aeruginosa Pterygium excision Nasal (35.5) 30 yrs 20/30 20/60 Scleral debridement, Choroidal detachment, posterior scleral patch graft, synechiae, nuclear sclerotic conjunctival ﬂap cataract, transient hypotony 4/M/79/R† P. aeruginosa Conjunctival excision Temporal (200) 2 yrs LP 1/200 Amniotic membrane Endophthalmitis, death because and radiotherapy for graft of chronic lymphocytic recurrent squamous leukemia cell carcinoma 5/M/82/R S. aureus Trabeculectomy Inferior (5.5) 1 mo 20/40 20/50 None None 6/F/71/L S. apiospermum Cataract extraction Nasal (13.5) 1 yr 20/70 20/100 Amniotic membrane Vitreitis, recrudescent scleritis, graft, conjunctival cystoid macular edema ﬂap

*Latent period is the time from surgery to symptomatic onset of scleritis. †Patient 4 had systemic immunosuppression secondary to chronic lymphocytic leukemia. No other patients had a non-ocular medical history, review of systems, or active medication use that would predispose to secondary infection. F, female; L, left; LP, light perception; M, male; R, right. keratitis for more than 11 years (approximately 1 patient with patient was improving when he developed leukemic compli- microbial anterior scleritis every 1.8 years). The initial visual cations and was lost to ophthalmologic follow-up. Final visual acuity at the time of diagnosis ranged from 20/40 to light acuity ranged from 20/20 to 20/60 for 4 eyes, 20/100 for 1, and perception. Each individual had previously undergone surgery worse than 20/400 for 1 (Table 1). of the affected eye, which included pterygium excision with b-irradiation (3), conjunctival squamous carcinoma excision with b-irradiation (1), trabeculectomy (1), and cataract CASE REPORTS extraction (1). Microbial isolates included Pseudomonas aeruginosa (2), Streptococcus pneumoniae (2), Staphylococ- Case 1 cus aureus (1), and Scedosporium apiospermum/Pseudalle- A 46-year-old woman presented with necrotizing suppurative scheria boydii (1). scleral ulceration, inferior exudative retinal detachment, and visual Endophthalmitis, defined as intraocular inflammation acuity of 20/40 of her left eye. She had undergone a nasal pterygium excision with b-irradiation 51 months previously. Initial treatment with microbial recovery from aqueous or vitreous specimens, included hourly moxifloxacin 0.5%, subconjunctival ceftazidime occurred in 2 patients with pseudomonal scleritis. One of these 25 mg, oral moxifloxacin, and oral prednisone. Scleral scrapings patients was treated with intravitreal antibiotics and the other yielded S. pneumoniae. Complete resolution of scleral inflammation was treated with subconjunctival tobramycin and systemic occurred over a 10-week-period, and no surgical intervention was ciprofloxacin. One patient with fungal scleritis had vitreitis, performed. but intraocular fluids were not examined. Other transient complications included exudative retinal detachment (1), Case 2 cystoid macular edema (1), choroidal detachment (1), and A 62-year-old man presented 1 month after excision of a nasal hypotony (1). Of these complications, there was complete pterygium with severe right eye pain, purulent scleral necrosis, and resolution of the hypotony and exudative retinal and choroidal adjacent scleral abscesses (Fig. 1). Initial treatment included detachments. superficial sclerectomy with subconjunctival ceftazidime 25 mg, All patients were initially administered a combination of hourly topical ceftazidime 5% and moxifloxacin 0.5%, and oral a topical cephalosporin and a topical aminoglycoside, amoxicillin. Scleral scrapings yielded S. pneumoniae. After repeat fluoroquinolone, or vancomycin. Topical natamycin was debridement, ocular inflammation subsided, and medications were begun when fungal filaments were recognized on smears of discontinued after 2 weeks of therapy. scleral scrapings. Three patients were administered subconjunctival or sub-Tenon injections of ceftazidime (2) or Case 3 tobramycin (1). Five patients received oral ciprofloxacin (2), A 73-year-old man presented with a painful scleral plaque and moxifloxacin (1), amoxicillin (1), or voriconazole (1). Topical 20/30 visual acuity (Fig. 2A) 30 years after nasal pterygium excision prednisolone acetate 1% was added during antibacterial with b-irradiation of the right eye. A hypopyon developed over the next week, and scleral scrapings and an anterior chamber aspirate treatment for 4 eyes with bacterial scleritis, and 2 also yielded P. aeruginosa. Initial treatment included hourly ceftazidime received oral prednisone. Surgical interventions included 5% and ciprofloxacin 0.3%, subconjunctival tobramycin 20 mg, and lamellar sclerectomy (1), scleral patch graft (1), and amniotic twice-daily oral ciprofloxacin. A scleral patch graft with rotating membrane graft (2) with or without a conjunctival flap. Five conjunctival flap was subsequently performed for residual scleral patients had complete resolution of ocular infection, and 1 thinning (Fig. 2B). Final visual acuity was 20/60. q 2011 Lippincott Williams & Wilkins www.corneajrnl.com | 1021 Cunningham et al Cornea Volume 30, Number 9, September 2011

We typically used a regimen of broad-spectrum antimicrobials that was modified based on microbial recovery. Topical therapy was often supplemented with subconjunctival and systemic agents.10,15 Most cases are because of Pseudomonas, staphylococci, and streptococci, although other bacteria are occasionally encountered. Fungi such as Scedosporium sp. are also capable of infecting the sclera.18,19 Among available antifungal agents, voriconazole has proved useful in controlling ocular scedosporiosis20,21 and other causes of fungal scleritis.22 Medical therapy aims to control microbial proliferation, but surgical intervention can be appropriate for some eyes. Debridement and sclerectomy debulk necrotic tissue and may facilitate antibiotic access.23 A patch graft helps to restore structural integrity of the globe.24 Although vascularization FIGURE 1. Case 2. S. pneumonia scleritis after pterygium might speed the resolution of infection, we generally defer surgery. A large scleral nasal abscess with associated purulent conjunctival flap and other grafting procedures until scleral material noted centrally. After sclerectomy and drainage with inflammation is medically controlled. subconjunctival, topical, and oral antibiotics, there was Adjunctive corticosteroid use remains controversial in complete resolution of the scleritis 14 days after initiation of the management of corneal and scleral infections.10,25 We the treatment. initiated topical and oral corticosteroids during the course of antibacterial therapy for patients with bacterial scleritis. DISCUSSION Although we did not encounter treatment-related adverse Microbial scleritis is an infrequent ocular infection. The effects, the role of immunosuppression in the management of prevalence of primary bacterial or fungal scleritis among patients scleral infectious disease remains uncertain but promising.26 with scleritis is estimated to be 1.7% in our cohort and in Vision-limiting sequelae of microbial scleritis include a previously reported case series.8 Scleral infection can cataract, exudative retinal detachment, choroidal effusion, commence a few weeks after anterior segment surgery or arise glaucoma, and phthisis bulbi. In recent case series, nearly one- decades later. Cataract extraction,9 trabeculectomy,10 and pars fourth of the eyes with microbial scleritis were removed plana vitrectomy11,12 have preceded infectious scleritis. However, because of progressive inflammation and other complica- based on our experience and recent case reports, pterygium tions.9,10,23,27,28 Enucleation during scleritis may be more likely excision seems to be the most common procedure predisposing with pyogenic scleral infection than granulomatous vasculi- to microbial anterior scleritis.3,13–17 Although not a prerequisite tis.29 Good vision has previously been obtained in only for scleral infection, adjunctive use of irradiation or antimeta- approximately half of the treated patients,9,10,27,28 but 5 of 6 bolites adds to the risk of scleral thinning and avascular necrosis eyes in this study regained visual acuity better than 20/200. that provide a nidus for microbial adherence.17 All patients who had good visual outcome had visual Specific treatment depends on the identification of acuity of 20/200 or better at the time of diagnosis, each had microorganisms from scleral specimens. Laboratory criteria intensive antibiotic management, and 3 patients underwent for culture-positive scleral infection have not yet been early surgical intervention. Although the limited number of adequately defined. Because of the retrospective nature of patients in our study precludes statistical analyses, a previous this study and the available microbiological data, bacterial or study also indicated that combined medical and surgical fungal growth on 1 or more primary culture media was used to management improved visual outcome compared with medical indicate culture positivity in this study. The development of treatment alone.28 The cumulative experience suggests that rapid diagnostic assays may enable estimation of the intensity better initial visual acuity correlates with a less intense ocular of the microbial load that could be used to guide treatment to infection, greater opportunity for therapeutic response, and predict outcome. better visual outcome.

FIGURE 2. Case 3. P. aeruginosa scleritis after pterygium surgery. A, Calcified scleral plaque with inflammation. B, After 8 weeks of antibacterial therapy, scleral patch graft with rotating conjunctival flap was performed.

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Effective management, guided by laboratory evaluation, 12. Rich RM, Smiddy WE, Davis JL. Infectious scleritis after retinal surgery. can improve the structural and visual outcome of microbial Am J Ophthalmol. 2008;145:695–699. 13. Moriarty AP, Crawford GJ, McAllister IL, et al. Severe corneoscleral scleritis. Antimicrobial agents, judicious surgical intervention, infection: a complication of beta irradiation scleral necrosis following and prudent antiinflammatory treatment offer the opportunity pterygium excision. Arch Ophthalmol. 1993;111:947–952. to control the inflammatory complications of infections 14. Lin CP, Shih MH, Su CY. Scleritis (letter). Surv Ophthalmol. 2006;51: affecting the sclera. 288–289. 15. Meallet MA. Subpalpebral lavage antibiotic treatment for severe infectious scleritis and keratitis. Cornea. 2006;25:159–163. ACKNOWLEDGMENTS 16. Lee JE, Oum BS, Choi HY, et al. Methicillin-resistant Staphylococcus The authors are grateful to Dr Milton Boniuk, who aureus sclerokeratitis after pterygium excision. Cornea. 2007;26: provided clinical information for one of the patients in this 744–746. report, and for the assistance of microbiologists at the Sid 17. Paula JS, Simaõ ML, Rocha EM, et al. Atypical pneumococcal scleritis after pterygium excision: case report and literature review. Cornea. 2006; W. Richardson Ocular Microbiology Laboratory and the 25:115–117. Methodist Hospital. 18. Singh RP, McCluskey P. Scedosporium prolificans sclerokeratitis 10 years after pterygium excision with adjunctive mitomycin C. Clin Experiment REFERENCES Ophthalmol. 2005;33:433–434. 1. Hemady R, Sainz de la Maza M, Raizman MB, et al. Six cases of scleritis 19. Jhanji V, Yohendran J, Constantinou M, et al. Scedosporium scleritis or associated with systemic infection. Am J Ophthalmol. 1992;114:55–62. keratitis or both: case series. Eye Contact Lens. 2009;35:312–315. 2. Ramesh S, Ramakrishnan R, Bharathi MJ, et al. Prevalence of bacterial 20. Shah KB, Wu TG, Wilhelmus KR, et al. Activity of voriconazole pathogens causing ocular infections in South India. Indian J Pathol against corneal isolates of Scedosporium apiospermum. Cornea. 2003; Microbiol. 2010;53:281–286. 22:33–36. 3. Su CY, Tsai JJ, Chang YC, et al. Immunologic and clinical manifestations 21. Bunya VY, Hammersmith KM, Rapuano CJ, et al. Topical and oral of infectious scleritis after pterygium excision. Cornea. 2006;25:663–666. voriconazole in the treatment of fungal keratitis. Am J Ophthalmol. 2007; 4. Moreno Honrado M, del Campo Z, Buil JA. A case of necrotizing scleritis 143:151–153. resulting from Pseudomonas aeruginosa. Cornea. 2009;28:1065–1067. 22. Fincher T, Fulcher SF. Diagnostic and therapeutic challenge of Aspergillus 5. Okhravi N, Odufuwa B, McCluskey P, et al. Scleritis. Surv Ophthalmol. flavus scleritis. Cornea. 2007;26:618–620. 2005;50:351–363. 23. Reynolds MG, Alfonso E. Treatment of infectious scleritis and 6. Wirostko WJ, Covert DJ, Han DP, et al. Microbiological spectrum of keratoscleritis. Am J Ophthalmol. 1991;112:543–547. organisms isolated from explanted scleral buckles. Ophthalmic Surg 24. Sangwan VS, Jain V,Gupta P.Structural and functional outcome of scleral Lasers Imaging. 2009;40:201–202. patch graft. Eye. 2006;21:930–935. 7. Biber JM, Schwam BL, Raizman MB. Scleritis. In: Krachmer JH, Mannis MJ, 25. Hindman HB, Patel SB, Jun AS. Rationale for adjunctive topical Holland EJ, eds. Cornea. 3rd ed. Philadelphia, PA: Mosby Elsevier; 2005: corticosteroids in bacterial keratitis. Arch Ophthalmol. 2009;127: 1253–1265. 97–102. 8. Foster CS, Sainz de la Maza M. The Sclera. New York, NY: Springer- 26. Lee GA, Gray TB, Dart JKG, et al. Acanthamoeba sclerokeratitis: Verlag; 1994:242–277. treatment with systemic immunosuppression. Ophthalmology. 2002;109: 9. Jain V,Garg P,Sharma S. Microbial scleritis–experience from a developing 1178–1182. country. Eye. 2009;23:255–261. 27. Hsiao CH, Chen JJY, Huang SCM, et al. Intrascleral dissemination of 10. Helm CJ, Holland GN, Webster RG, et al. Combination intravenous infectious scleritis following pterygium excision. Br J Ophthalmol. 1998; ceftazidime and aminoglycosides in the treatment of pseudomonal 82:29–34. scleritis. Ophthalmology. 1997;104:838–843. 28. Huang FC, Huang SP, Tseng SH. Management of infectious scleritis after 11. Feiz V,Redline DE. Infectious scleritis after pars plana vitrectomy because pterygium excision. Cornea. 2000;19:34–39. of methicillin-resistant Staphylococcus aureus resistant to fourth- 29. Riono WP,Hidayat AA, Rao NA. Scleritis: a clinicopathologic study of 55 generation fluoroquinolones. Cornea. 2007;26:238–240. cases. Ophthalmology. 1999;106:1328–1333.

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